The individual enzyme implicated in both oxidative phosphorylation and the tricarboxylic acid cycle is mitochondrial succinate dehydrogenase (SDH), often stated as electron transport chain complex II. Such metabolic enzymes are recognized to play a critical part in metabolic diseases. Due to its critical function in regulating mitochondrial metabolism and human health, SDH has drawn more and more attention. The finding of its function in human disease has rekindled interest in this complex, which has received the least amount of research on the mitochondrial respiratory complexes. SDH is recognized to perform a significant part in metabolic reprogramming, energy balancing and biosynthetic pathways. The lack of pancreatic β-cells and SDH compromises glucose-encouraged ATP formation, insulin secretion and β-cell development by mitochondrial membrane potential failure and impairs glucose-induced oxidative phosphorylation. Under pathological circumstances, SDH may potentially be a substantial generator of reactive oxygen species (ROS). We have previously revealed that elevated reactive oxygen species production is essential for the development of obesity. During the bacterial fermentation of dietary fibre, SDH is also generated at significant levels. In individuals with inflammatory bowel disease and intestinal swelling, elevated SDH levels have been observed in the gut lumen. It is unclear how SDH affects immune system inflammation in the gut mucosa, though. By describing its changes and dysfunctionality, we address the biology, pathophysiology and importance of the SDH enzyme in metabolic disorders in this book chapter.